I cover cardiology news for CardioExchange, a social media website for cardiologists published by the New England Journal of Medicine. I was the editor of TheHeart.Org from its inception in 1999 until December 2008. Following the purchase of TheHeart.Org by WebMD in 2005, I became the editorial director of WebMD professional news, encompassing TheHeart.Org and Medscape Medical News. Prior to joining TheHeart.Org, I was a freelance medical journalist and wrote for a wide variety of medical and computer publications. In 1994-1995 I was a Knight Science Journalism Fellow at MIT. I have a PhD in English from SUNY Buffalo, and I drove a taxicab in New York City before embarking on a career in medical journalism. You can follow me on Twitter at: @cardiobrief.

The Mediterranean Diet: The New Gold Standard?

Earlier today I summarized the important new PREDIMED study published in the New England Journal of Medicine showing the cardiovascular benefits of the Mediterranean diet. This study– a rare and much welcome instance of a large randomized controlled study of a diet powered to reach conclusions about important cardiovascular endpoints– has been widely praised and will undoubtedly have a major effect in the field of nutrition and will influence lots of people to adopt some form of a Mediterranean diet.

The study’s major potential weakness appears to be that the control group didn’t get a fair chance. Here’s how the authors describe the control group:

Participants in the control group… received dietary training at the baseline visit and completed the 14-item dietary screener used to assess baseline adherence to the Mediterranean diet. Thereafter, during the first 3 years of the trial, they received a leaflet explaining the low-fat diet (Table S2 in the Supplementary Appendix) on a yearly basis. However, the realization that the more infrequent visit schedule and less intense support for the control group might be limitations of the trial prompted us to amend the protocol in October 2006. Thereafter, participants assigned to the control diet received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean-diet groups, with the use of a separate 9-item dietary screener (Table S3 in the Supplementary Appendix).

Obviously this is not ideal, and it’s unclear whether any attempt to correct the problem after 3 years could be satisfactory. The study authors addressed this question in their discussion:

The lower intensity of dietary intervention for the control group during the first few years might have caused a bias toward a benefit in the two Mediterranean-diet groups, since the participants in these two groups received a more intensive intervention during that time. However, we found no significant interaction between the period of trial enrollment (before vs. after the protocol change) and the benefit in the Mediterranean-diet groups.

In an email, one of the study authors, Miguel Angel Martínez-González, explained this in slightly clearer language:

…after we increased our efforts to foster the adherence to the low-fat diet (beginning Oct 2006) the advantage of fat-rich Mediterranean diet was higher, with a hazard ratio much more impressive (0.49, 95%CI: 0.26 to 0.92) than when we did less efforts to promote the low-fat diet (0.77, 95%CI: 0.59-1.00). That cannot be interpreted in any way as a good reason to think that the result we found is due to not promoting the low-fat diet, but because of the superiority of the Mediterranean diets.

This seems like a reasonable response, but Dean Ornish, probably the best-known and most passionate advocate of low-fat diets, goes much further in attacking the credibility of the trial. In an article in the Huffington Post, he notes that at no time in the trial did the control group test a true low-fat diet.

In the “low-fat” group, total fat consumption decreased insignificantly, from 39 percent to 37 percent (Table S7, appendix). This doesn’t even come close to the American Heart Association guidelines of a low-fat diet (<30 percent fat) or ours for reversing heart disease (<10 percent fat).

So, they weren’t comparing a Mediterranean diet to a low-fat diet, because the control group was not following a low-fat diet. And I’m not talking about a very low-fat diet that we found (with other nutritional and lifestyle changes) could reverse heart disease, but even a moderately low-fat diet.

The authors should have concluded that the Mediterranean diet reduced cardiovascular risk when compared to whatever diet they were eating before, not when compared to a low-fat diet, since patients in the control group (“low-fat diet”) were not consuming a low-fat diet.

I think Ornish has a reasonable point here, but he has another much larger problem. It’s not clear– and it seems unlikely– that there could ever be a real world clinical trial testing the effect of an extreme Ornish-style low-fat diet. A few extremely dedicated individuals have been able to adopt, and perhaps benefit from, his severe diet, but I can’t imagine that a large, free-living population could ever endure the Ornish diet for more than a short period. Ornish has been advocating his diet for more than a generation now. He’s been criticized because his trials have only demonstrated the effects of his diet on surrogate or intermediate endpoints. But I think that before embarking on a large randomized controlled trial he first needs to demonstrate that such a trial would even be feasible.

The really great thing about the Mediterranean diet, by contrast, is that we know with 100% certainty that it is possible for people to live and eat this way, since they’ve been doing so for millennia. It’s true, though, that the new study didn’t really demonstrate that the Mediterranean diet is better than a true low-fat diet. But it did demonstrate that a Mediterranean diet is healthier than what most people are currently eating. So it’s a good example of a real world trial.

Ornish’s perspective is an extreme version of the anti-fat/low-fat viewpoint. The best known and more moderate version comes from the American Heart Association. In response to the study news today the AHA reminded people about its own somewhat complicated and shifting perspective on the Mediterranean diet and dietary fats. (Click here for the statement.) Here’s how the AHA compares their diet to the Mediterranean diet:

Mediterranean-style diets are often close to our dietary recommendations, but they don’t follow them exactly. In general, the diets of Mediterranean peoples contain a relatively high percentage of calories from fat. This is thought to contribute to the increasing obesity in these countries, which is becoming a concern.

The AHA statement concludes:

Before advising people to follow a Mediterranean diet, we need more studies to find out whether the diet itself or other lifestyle factors account for the lower deaths from heart disease.

But the AHA fails to note that there have been no big randomized clinical trials with hard outcomes that show the benefit of their diet. Now that the Spanish PREDIMED study has been published, I think it must be considered the gold standard. Now it is up to the AHA, and Ornish, to prove that their diets are better than, or even as good as, the Mediterranean diet.

There’s one other possibility to consider here. It’s possible that we’ve made this issue far too complex. After all, the Spanish investigators acknowledge that they didn’t really make very big or significant changes in the diets of any of their subjects, either in the Mediterranean diet or in the control groups. The only really big difference is that they gave olive oil and nuts to people in the Mediterranean diet subgroups. Perhaps this is the key lesson. Instead of getting lost in the weeds hunting for clues to a metabolic mystery, perhaps we should think about diet more simply as a public health issue. Make healthy foods available to people. If people substitute walnuts or olive oil for a candy bar or french fries then they will benefit.

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A closer look at the assigned diets shows another important difference: the “low fat” group was encouraged to eat pasta and other carbohydrates. The carbohydrates substitute for the fat calories in the Mediterranean diet group. Pretty much all the recent studies comparing diets with different proportions of carbohydrates and fats have shown those with higher fat ratio to be healthier.

Ornish and the American Heart Association still have to prove their diets are better than low carbohydrate diets too.

Aren’t you concerned that there were actually less all-cause mortality in the control group, there was certainly no significant diff in all-cause-mortality. Moreover there is no statistically significant difference in any of the “secondary endpoints” (i.e. the ones that people care about) besides slight diff in stroke, but there is some significant diff only in some syntheticall variables, which are called “primary endpoints”. I think the conclusions of this trial are weird, considering the disappointing results.

No, not concerned. The trial was not powered for all-cause mortality, and in a relatively young and healthy population it would be surprising if it had shown a difference in mortality after only 5 years. The same concepts holds for the secondary endpoints.

The main point here is that the trial was expressly designed to examine cardiovascular outcomes as defined by the primary endpoint. When it comes to diet trials, this is about as good as it gets. Of course we would always like to see more and better data, but in truth a randomized controlled trial in this field is very rare, so we are lucky to have even this.

I think it is a bit avoiding the issue. The mean age is 67 at start of trial (+5 yrs is 72), which is not young. Neither they are healthy, a lot of the participants have all the risk factors, hypertension, weight,. dyslipedimia and also family history. And indeed there is a non negligible mortality, but which is not significant to any direction. In addition, correct me if I am wrong, the “primary-outcomes” are just a mathematical variable comprised of some weighting and manipulation of the “secondary-outcomes”.

They write: “The primary end point was a composite of myocardial infarction, stroke, and death from cardiovascular causes. Secondary end points were stroke, myocardial infarction, death from cardiovascular causes, and death from any cause.”

None of the “real-outcomes” (how I would call them – the one people care about) beside stroke have any statistical significance.

As already noted in other places, it is a small effect, in an observational study, discounting treatment effect (the study seems to be designed to show treatment effect) – there simply might not be any signal there.

The perfect trial will never happen. This is an example of a really good trial, however. The effect seen in the trial is roughly equivalent to the effect seen with statins, as others have pointed out. That’s really huge news, IMO. And what’s the downside to the Mediterranean Diet? This is not a drug, this is an attractive lifestyle. We don’t need to calculate a risk/benefit analysis because the risk is nonexistent.

I can’t address at length here the question about endpoints, but a composite outcome like this is standard practice in clinical trials. In this case it’s not fair that the trial didn’t show statistical significance for each of the individual components or for the secondary endpoints. The trial simply wasn’t designed to measure these separately. To do so would have required a much larger trial lasting a much longer time. I think we should congratulate the investigators for performing an significant, real-world trial with important implications for lots of people. That’s about as good as it gets.

I´m glad to read this news! Today olive oil is one of the most popular edible oils worldwide both for its nutritional value as for its high gastronomic qualities. Its high content of unsaturated fatty acids, vitamin E, natural antioxidants and other nutrients make medical science considers as one of the healthiest. There are many studies showing the benefits of the Mediterranean diet on weight control, cancer prevention breast, cerebro-vascular accidents, from heart attacks and anaemia, among other diseases. The Mediterranean diet besides being varied and balanced nutritional intake, is rich in fiber, unsaturated fatty acids and antioxidants. More than a diet, is said to be a way of life, which to generate a positive effect obviously be combined with moderate exercise daily.I invite you to learn more about the Mediterranean diet by visiting: goo.gl/I5FKH

I´m glad to read this news! Today olive oil is one of the most popular edible oils worldwide both for its nutritional value as for its high gastronomic qualities. Its high content of unsaturated fatty acids, vitamin E, natural antioxidants and other nutrients make medical science considers as one of the healthiest. There are many studies showing the benefits of the Mediterranean diet on weight control, cancer prevention breast, cerebro-vascular accidents, from heart attacks and anaemia, among other diseases. The Mediterranean diet besides being varied and balanced nutritional intake, is rich in fiber, unsaturated fatty acids and antioxidants. More than a diet, is said to be a way of life, which to generate a positive effect obviously be combined with moderate exercise daily.I invite you to learn more about the Mediterranean diet by visiting: goo.gl/I5FKH

The Mediterranean diet has proven to be the most healthy and balanced diets in the world. The main elements of that diet are vegetables, fish, olive oil and wine in moderation. Very important is that we can consume up to four eggs a week. In addition, the diet is rich in fish and seafood, which are a great source of Omega – 3 fatty acids. Although it is high in fat (about 35% of the calories that are taken), it is low in animal fat (7-8%). Unlike, it is preferred the olive oil, which increases the level of good cholesterol – the HDL. The wine should be consumed in moderation – one to two glasses daily with a meal. The main advantage of the Mediterranean diet is the abundance of antioxidants, fiber and omega-3 fatty acids. If someone watches, the calorie intake, he would see in a short time a great improvement in his health.

I wonder if anyone is looking at the effects of Vitamin D on CV risks…sun exposure might prove to be equally important as diet. Diet studies and their correlation with CV events might be useful in Scandinavia as well.

The Mediterranean Diet is always superb for improving health. But what makes them better are the healthy food ingredients found in the Mediterranean area. Otherwise, the only work of each food is to provide the energy what our body requires on a daily basis.